Laser-scanning confocal microscopy has become an indispensable tool in biomedicine, driven by the advent of powerful new microscope systems and of wide range of specific fluorescent probes. Currently, state-of-the art confocal microscopy is required for NIH- funded projects at Downstate Medical Center. We propose to acquire a Leica TCS SP5 laser scanning confocal system to replace the existing Bio-Rad confocal microscope, currently maintained by Zeiss imaging. Zeiss is discontinuing the BioRad line and will not provide service after October 2009. The requested Leica microscope will be the only confocal system not only in the Institution but also in Brooklyn. Therefore, the new purchase will be a vital component of our facility. The BioRad microscope is used 36-40 hours per week and has been maintained using resources provided by the School of Medicine. We determined that a Leica TCS SP5 would provide the fast scan rates, high resolution, high sensitivity to reduce light load and damage to cells, and ability to fine tune excitation and emission channels to aid in simultaneous acquisition of multiple fluorescence channels needed for seven major NIH-funded projects as well as minor projects, outlined in this proposal. The investigators identified as Major Users in this grant have been selected for their current and future requirement for advanced confocal imaging, significant degree of NIH funding, and potential benefit from acquisition a high-end confocal to replace an instrument that is being discontinued. The Leica SP5 confocal microscope will be maintained at the Cell Imaging Core facility located in the Dept of Anatomy and Cell Biology of SUNY-Downstate Medical Center. This facility now houses the Bio-Rad microscope. The facility has two full-time staff including the director (Ph.D.), and a microscopy technician. The sole responsibility of the staff is to maintain the instruments, develop new imaging and image processing techniques, and train users. The research interests of our faculty encompass a broad range of subjects within cell biology and physiology and neuroscience. The focus is on fundamental research in lipid metabolism, vision research, signal transduction, regulation of cell cycle, hypertension, cancer and diabetes. Cellular imaging is an essential tool used by our faculty to carry out their diverse research projects.